摘要
目的:探讨3%地夸磷索钠滴眼液治疗干眼前后自觉症状改善与体征变化的关系。方法:多中心、前瞻性及大样本的Ⅳ期临床试验研究。纳入2019年5月至2021年6月在首都医科大学附属北京同仁医院眼科中心等30家眼科机构就诊的干眼患者2660例(2660只眼)。其中，男性680例(680只眼)，女性1980例(1980只眼)；年龄21～69岁，平均年龄(44.0±15.3)岁。所有患者使用3%地夸磷索钠滴眼液单药治疗，1滴/1次点眼，6次/d，治疗30 d。于治疗前、治疗后14 d及治疗后30 d时行裂隙灯显微镜、泪膜破裂时间(BUT)、角膜荧光素染色(CFS)及Schirmmer Ⅰ试验(SⅠt)等体征检查和干眼相关生活质量评分(DEQS)等自觉症状评估。DEQS总分和总体感觉评分符合正态分布，采用±s表示，两组比较采用独立样本t检验，多组比较采用单因素方差分析，当差异有统计学意义时，采用SNK法进行两两比较。治疗后自觉症状改善与体征变化的相关性分析采用Pearson相关分析。结果:治疗14 d和30 d后，BUT>5 s组患者DEQS总分和总体感觉改善分别为(－17.57±17.29)分、(－20.15±17.39)分、(－1.00±0.89)分及(－1.00±0.89)分；BUT≤5 s组患者DEQS总分和总体感觉改善分别为(－12.36±15.67)分、(－14.38±16.07)分、(－0.70±0.82)分及(－0.70±0.80)分，组间患者DEQS总分改善差异均有统计学意义(t＝－2.87，－3.34；P<0.05)。SⅠt>10 mm组、5 mm<SⅠt≤10 mm组及SⅠt≤5 mm组患者DEQS总体感觉改善分别为(－0.60±0.72)分、(－0.80±0.82)分、(－0.80±0.77)分、(－1.00±0.86)分、(－0.80±0.87)分及(－1.10±0.93)分；总分改善分别为(－9.83±12.95)分、(－15.37±15.32)分、(－14.32±15.22)分、(－20.14±16.80)分、(－13.75±17.36)分及(－18.72±18.57)分，组间总体感觉改善的差异均有统计学意义(F＝23.68，23.31，18.36，14.80；P<0.05)。1分≤CFS评分<6分、6分≤CFS评分<10分及≥10分组患者DEQS总体感觉改善分别为(0.70±0.80)分、(0.90±0.87)分、(0.90±0.85)分、(1.20±0.95)分、(0.90±0.78)分及(0.80±0.70)分；DEQS总分改善分别为(12.69±15.73)分、(17.82±17.10)分、(13.87±12.67)分、(20.39±18.55)分、(9.45±11.13)分及(13.55±12.41)分。除治疗14 d后DEQS总分改善组间差异无统计学意义(F＝1.62，P>0.05)外，其余组间差异均有统计学意义(F＝16.25，18.80，5.09；P<0.05)。治疗14 d和治疗30 d后，≥60岁组患者DEQS总分与本研究全部检查的体征变化的相关性均具有统计学意义(|r|＝0.35，0.49，0.33，0.33，0.40，0.33；P<0.05)；DEQS总体感觉与BUT和SⅠt变化的相关性均具有统计学意义(|r|＝0.54，0.34，0.47，0.33；P<0.05)。男性组DEQS总分评分变化与CFS变化的相关性均具且有统计学意义(|r|＝0.31，0.31；P<0.05)；总体感觉与BUT变化相关，且有统计学意义(|r|＝0.46，0.32；P<0.05)。结论:治疗后干眼患者随体征变化和患者的自觉症状多可获得改善。干眼患者干眼自觉症状和体征与患者的年龄及性别无相关性，表现为症状体征分离。治疗后60岁及以上年龄组患者的自觉症状改善与体征变化相关；治疗后短期男性患者自觉症状改善与CFS及BUT改善相关。
Abstract
Objective:To evaluate the correlation between changes of subjective symptoms and objective signs before and after 3% diquafosol sodium eye drops treatment in patients with dry eyes.Methods:This was a multi-center, prospective large scale phase Ⅳ clinical trial. A total of 2660 patients (2660 eyes) with dry eye were included in Beijing Tongren Eye Center, Beijing Tongren Hospital affiliated with Capital Medical University and others 30 ophthalmology clinics nationwide from May 2019 to June 2021. Among them, there were 680 males (680 eyes) and 1980 females (1980 eyes), aged 21 to 69 years with an average age of (44.0±15.3) years. Patients were treated with 3% diquafosol sodium eye drops 6 times a day alone for 30 days. The objective signs, including slit-lamp microscopic examination, tear film breakup time (BUT), corneal fluorescein staining (CFS), Schirmer Ⅰ test (SⅠt) and subjective symptoms, including dry eye-related quality-of-life score (DEQS), were perfomed before and after treatment for 14 days and 30 days. The DEQS total score and DEQS total perception followed a normal distribution and were expressed as ±s, compared by independent sample t-test between two groups, and by one-way analysis of variance among multiple groups. When the difference was statistically significant, SNK method was further used for pairwise comparison. Pearson correlation analysis was used to analyze the correlation between changes of subjective symptoms and objective signs after treatment.Results:After treatment for 14 days and 30 days, the changes of DEQS total score and DEQS total perception in BUT>5 s subgroup were(-17.57±17.29)scores, (-20.15±17.39)scores, (-1.00±0.89)scores, (-1.00±0.89)scores, respectively; the changes in BUT≤5 s subgroup were (-12.36±15.67)scores, (-14.38±16.07)scores, (-0.70±0.82)scores, (-0.70±0.80)scores, respectively. There were significant differences in changes of DEQS total score between two groups (t=-2.87, -3.34; P<0.05). After treatment for 14 days and 30 days, the changes of DEQS total perception in SⅠt>10 mm, 5 mm<SⅠt≤10 mm, SⅠt≤5 mm subgroup were (-0.60±0.72)scores, (-0.80±0.82)scores, (-0.80±0.77)scores, (-1.00±0.86)scores, (-0.80±0.87)scores, (-1.10±0.93)scores, respectively; the changes of DEQS total score were (-9.83±12.95)scores, (-15.37±15.32)scores, (-14.32±15.22)scores, (-20.14±16.80)scores, (-13.75±17.36)scores, (-18.72±18.57)scores, respectively. There were significant differences in improvements of DEQS total perception in different SⅠt subgroups (F=23.68, 23.31, 18.36, 14.80; P<0.05). After treatment for 14 days and 30 days, the changes of DEQS total perception in (0.70±0.80)scores, (0.90±0.87)scores, (0.90±0.85)scores, (1.20±0.95)scores, (0.90±0.78)scores, and (0.80±0.70)scores, respectively; the changes of DEQS total score were (12.69±15.73)scores, (17.82±17.10)scores, (13.87±12.67)scores, (20.39±18.55)scores, (9.45±11.13)scores and (13.55±12.41)scores, respectively. Except for no statistically significant improvement in the DEQS total score after treatment for 14 days (F=1.62, P>0.05), other intergroup comparisons were all statistically significant (F=16.25, 18.80, 5.09; P<0.05). After treatment, there was a correlation with between DEQS total score and different clinical manifestations in ≥60 years subgroup, with a statistically significant difference (|r|=0.35, 0.49, 0.33, 0.33, 0.40, 0.33; P<0.05). There was a correlation with between DEQS total perception and BUT, SⅠt in age≥60 years subgroup, with a statistically significant difference (|r|=0.54, 0.34, 0.47, 0.33; P<0.05). There was a correlation with between DEQS total score and CFS in male subgroup, with a statistically significant difference (|r|=0.31, 0.31; P<0.05). There was a correlation with between DEQS total perception between DEQS total perception and BUT in male subgroup, with a statistically significant difference (|r|=0.46, 0.32; P<0.05).Conclusions:After treatment, with the improvement of physical signs, patients with different dry eyes show the corresponding improvements in the subjective symptoms. There is no correlation between signs and symptoms of dry eye in different groups of ages or sex before treatment, indicating a separation of signs and symptoms. After treatment, the changes of subjective symptoms has correlation with the improvments of objective signs in age≥60 years subgroup. After short-term treatment, the changes of subjective symptoms has correlation with the improvments of CFS and BUT in male subgroup.
万方数据